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Pesticide residues in food - 2003 - Joint FAO/WHO Meeting on Pesticide Residues

WHO/PCS/04.1

Toxicological evaluations

Sponsored jointly by FAO and WHO
With the support of the International Programme
on Chemical Safety (IPCS)

Joint Meeting of the
FAO Panel of Experts on Pesticide Residues
in Food and the Environment
and the
WHO Core Assessment Group

Geneva, Switzerland, 15-24 September 2003

The summaries and evaluations contained in this book are, in most cases, based on unpublished proprietary data submitted for the purpose of the JMPR assessment. A registration authority should not grant a registration on the basis of an evaluation unless it has first received authorization for such use from the owner who submitted the data for JMPR review or has received the data on which the summaries are based, either from the owner of the data or from a second party that has obtained permission from the owner of the data for this purpose.

WORLD HEALTH ORGANIZATION

WHO Library Cataloguing-in-Publication Data

Joint Meeting of the FAO Panel of Experts on Pesticides Residues in Food and the Environment and the WHO Core Assessment Group (2003: Geneva, Switzerland). Pesticide residues in food: 2003: toxicological evaluations/Joint Meeting of the FAO Panel of Experts on Pesticides Residues in Food and the Environment and the WHO Core Assessment Group, Geneva, 15-24 September 2003.

1.Pesticide residues—toxicity 2.Food contamination 3.No-observed-adverse-effect level
I. FAO Panel of Experts on Pesticides Residues in Food and the Environment
II.WHO Core Assessment Group on Pesticide Residues III.Title

ISBN 92 4 166519 X  (NLM classification: WA 240)

This report contains the collective views of two international groups of experts and does not necessarily represent the decisions nor the stated policy of the Food and Agriculture Organization of the United Nations or the World Health Organization.

The preparatory work for the toxicological evaluations of pesticide residues carried out by the WHO Expert Group on Pesticide Residues for consideration by the FAO/WHO Joint Meeting on Pesticide Residues in Food and the Environment is actively supported by the International Programme on Chemical Safety within the framework of the Inter-Organization Programme for the Sound Management of Chemicals.

The International Programme on Chemical Safety (IPCS), established in 1980, is a joint venture of the United Nations Environment Programme (UNEP), the International Labour Organisation (ILO), and the World Health Organization (WHO). The overall objectives of the IPCS are to establish the scientific basis for assessing the risk to human health and the environment to exposure from chemicals, through international peer-review processes as a prerequisite for the promotion of chemical safety, and to provide technical assistance in strengthening national capacities for the sound management of chemicals.

The Inter-Organization Programme for the Sound Management of Chemicals (IOMC) was established in 1995 by UNEP, the Food and Agriculture Organization of the United Nations, WHO, the United Nations Industrial Development Organization, and the Organisation for Economic Co-operation and Development (Participating Organizations), following recommendations made by the 1992 United Nations Conference on the Environment and Development to strengthen cooperation and increase coordination in the field of chemical safety. The purpose of the IOMC is to promote coordination of the policies and activities pursued by the Participating Organizations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment.

© World Health Organization 2004

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TABLE OF CONTENTS

List of participants

Abbreviations

Introduction

Toxicological evaluations

Carbosulfan**

Cyprodinil*

Dimethoate

Famoxadone*

Malathion

Methoxyfenozide*

Paraquat**

Phosmet

Pyraclostrobin*

Pyrethrins

Tebufenozide

Terbufos**

Annex 1. Reports and other documents resulting from previous Joint Meetings of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Groups on Pesticide Residues

* First full evaluation

** Evaluated within the periodic review programme of the Code Committee on Pesticide Residues

2003 Joint Meeting of the FAO Panel of Experts on
Pesticide Residues in Food and the Environment
and the WHO Core Assessment Group

Geneva, 15-24 September 2003

PARTICIPANTS

FAO Panel of Experts on Pesticide Residues in Food and the Environment

Dr U. Banasiak, Federal Institute for Risk Assessment, Berlin, Germany

Dr E. Dutra Caldas, University of Brasilia, College of Health Sciences, Pharmaceutical Sciences Department, Brasilia/DF, Brazil (FAO Rapporteur)

Dr S. Funk, Health Effects Division, United States Environmental Protection Agency, Washington DC, USA (Vice-Chairman)

Mr D.J. Hamilton, Principal Scientific Officer, Animal & Plant Health Service, Department of Primary Industries, Brisbane, Australia

Dr B.C. Ossendorp, Centre for Substances and Integrated Risk Assessment, National Institute of Public Health and the Environment (RIVM), Bilthoven, Netherlands

Dr Y. Yamada, Research Planning and Coordination Division, National Food Research Institute, Tsukuba, Japan

WHO Toxicological Core Assessment Group

Professor A.R. Boobis, Experimental Medicine and Toxicology, Division of Medicine, Faculty of Medicine, Imperial College London, England (WHO Chairman)

Dr L. Davies, Science Strategy—Pesticides, Office of Chemical Safety, Australian Department of Health and Ageing, Woden, Australia

Dr V.L. Dellarco, United States Environmental Protection Agency, Office of Pesticide Programs, Health Effects Division, Washington DC, USA (WHO Rapporteur)

Dr H. Hakansson, Institute of Environmental Medicine, Karolinska Institute, Unit of Environmental Health Risk Assessment, Stockholm, Sweden

Dr A. Moretto, Dipartimento Medicina Ambientale e Sanità Pubblica, Università di Padova, Padova, Italy

Dr R. Solecki, Pesticides and Biocides Division, Federal Institute for Risk Assessment Thielallee, Berlin

Dr M. Tasheva, Laboratory of Toxicology, National Centre of Hygiene, Medical Ecology and Nutrition, Sofia, Bulgaria

Secretariat

Dr A. Ambrus, Head, Agrochemicals Unit, Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, International Atomic Energy Agency, Vienna, Austria (FAO Consultant)

Dr A. Bartholomaeus, Therapeutic Goods Administration, Australian Department of Health and Ageing, Woden, Australia (WHO Temporary Adviser)

Mr B. Declercq, Ministère de l'Economie et des Finances, Laboratoire interrégional de la DGCCRF, Massy, France (FAO Consultant)

Dr I.C. Dewhurst, Pesticides Safety Directorate, King's Pool, York, England (WHO Temporary Adviser)

Dr S. Dogheim, Agriculture Research Centre, Ministry of Agriculture, Heliopolis, Cairo, Egypt (FAO Consultant)

Dr K. Hamernik, Office of Science Coordination and Policy, United States Environmental Protection Agency, Washington DC, USA (WHO Temporary Adviser)

Mr A.R.C. Hill, Department for Environment, Food and Rural Affairs, Central Science Laboratory, Sand Hutton, York, England (FAO Consultant)

Dr H. Jeuring, Chairman, Codex Committee on Pesticide Residues, Senior Public Health Officer Food, Food and Consumer Product Safety Authority, The Hague, Netherlands (WHO Temporary Adviser)

Mr D. Lunn, Programme Manager (Residues-Plants), Dairy and Plant Products Group, New Zealand Food Safety Authority, Wellington, New Zealand (FAO Consultant)

Dr D. MacLachlan, Australian Quarantine and Inspection Service, Australian Department of Agriculture, Fisheries and Forestry, Edmond Barton Building, Kingston, Australia (FAO Consultant)

Ms S. Malezieux, Ministère de l'agriculture, de la pêche, de l'alimentation et des affairs rurales, Direction Genérale de l'Alimentation, Paris, France (FAO Consultant)

Dr T.C. Marrs, Food Standards Agency, London, England (WHO Temporary Adviser)

Dr J. Maskeliunas, Food Standards Officer, Joint FAO/WHO Food Standards Programme, Food and Nutrition Division, Food and Agriculture Organization of the United Nations, Rome, Italy (FAO Staff Member)

Dr D.B. McGregor, Lyon, France (WHO Temporary Adviser)

Dr G. Moy, Food Safety Programme, World Health Organization, Geneva, Switzerland (WHO Staff Member)

Dr S. Page, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland (WHO Staff Member)

Dr R. Pfeil, Pesticides and Biocides Division, Federal Institute for Risk Assessment, Berlin, Germany (WHO Temporary Adviser)

Dr P.V. Shah, US Environmental Protection Agency, Washington DC, USA (WHO Temporary Adviser)

Dr A. Takagi, Division of Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setaga-ku, Tokyo, Japan (WHO Temporary Adviser)

Dr A. Tejada, FAO Joint Secretary to JMPR Pesticide Management Group, Plant Protection Service, Plant Production and Protection Division, Food and Agriculture Organization of the United Nations, Rome, Italy (FAO Joint Secretary)

Dr A. Tritscher, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland (WHO Joint Secretary)

Dr G. Vaagt, Senior Officer, Pesticide Management Group, Food and Agriculture Organization of the United Nations, Rome, Italy (FAO Staff Member)

Dr Gerrit Wolterink, Centre for Substances and Risk Assessment, National Institute of Public Health and the Environment (RIVM), Bilthoven, Netherlands (WHO Temporary Adviser)

Abbreviations used

ADI

acceptable daily intake

ai

active ingredient

AUC

area under the curve for concentration-time

bw

body weight

CCN

Codex classification number (for compounds or commodities)

CCPR

Codex Committee on Pesticide Residues

CYP

cytochrome P450

CXL

Codex level

DMSO

dimethyl sulfoxide

ECD

electron capture detection

F0

parental generation

F1

first filial generation

F2

second filial generation

FAO

Food and Agricultural Organization of the United Nations

FOB

functional observational battery

GC

gas chromatography

GCP

good clinical practice

GLC

gas-liquid chromatography

GLP

good laboratory practice

GPC

gel-permeation chromatography

GEMS/Food

Global Environment Monitoring System-Food Contamination Monitoring and Assessment Programme

GSH

glutathione

HPLC

high-performance liquid chromatography

IARC

International Agency for Research on Cancer

IEDI

international estimated daily intake

IESTI

international estimate of short-term dietary intake

ISO

International Standards Organization

JECFA

Joint Expert Committee on Food Additives

JMPR

Joint Meeting on Pesticide Residues

LC

liquid chromatography

LC50

median lethal concentration

LD50

median lethal dose

LOAEL

lowest-observed-adverse-effect level

LOAEC

lowest-observed-adverse-effect concentration

LOD

limit of detection

LOQ

limit of quantification

MDL

method detection limit

MLD

minimum level of detection

MRL

maximum residue limit

MS

mass spectrometry

MS/MS

tandem mass spectrometry

NAD

nicotinamide adenine dinucleotide

NADP

nicotinamide adenine dinucleotide phosphate

NADPH

nicotinamide adenine dinucleotide phosphate, reduced form

NOAEL

no-observed-adverse-effect level

NOEL

no-observed-effect level

OECD

Organization for Economic Co-operation and Development

RfD

reference dose

TMDI

theoretical maximum daily intake

UV

ultraviolet radiation

WHO

World Health Organization

Introduction

The toxicological monographs and monograph addenda contained in this volume were prepared by a WHO Core Assessment Group that met with the FAO Panel of Experts on Pesticide Residues in Food and the Environment in a Joint Meeting on Pesticide Residues (JMPR) in Geneva, Switzerland, on 15-24 September 2003.

Four of the compounds evaluated by the Core Assessment Group at the Meeting, cyprodinil, famoxadone, methoxyfenozide and pyraclostrobin, were evaluated for the first time. The other eight substances had been evaluated at previous meetings. For five of these, only information received since the previous evaluations is summarized in "monograph addenda". Of these, dimethoate, malathion, phosmet and tebufenozide were evaluated for establishment of an acute reference dose. The appropriate earlier documents on the five compounds should be consulted in order to obtain full toxicological profiles. Toxicological monographs were prepared on carbosulfan, paraquat and terbufos, summarizing new data and, where relevant, incorporating information from previous monographs and addenda. Reports and other documents resulting from previous Joint Meetings on Pesticide Residues are listed in Annex 1.

The report of the Joint Meeting has been published by the FAO as FAO Plant Production and Protection Paper 176. That report contains comments on the compounds considered, acceptable daily intakes established by the WHO Core Assessment Group, and maximum residue limits established by the FAO Panel of Experts. Monographs on residues prepared by the FAO Panel of Experts are published as a companion volume, as Evaluations 2003, Part I, Residues, in the FAO Plant Production and Protection Paper series.

The toxicological monographs and addenda contained in this volume are based on working papers that were prepared by temporary advisers before the 2003 Joint Meeting. A special acknowledgement is made to those advisers. The monographs were edited by Dr H. Mattock, St Jean d'Ardières, France.

The preparation and editing of this volume was made possible by the technical and financial contributions of the lead institutions of the International Programme on Chemical Safety (IPCS), which supports the activities of the JMPR. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Central Unit of the IPCS concerning the legal status of any country, territory, city or area or of its authorities, nor concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the IPCS in preference to others of a similar nature that are not mentioned.

Any comments or new information on the biological properties or toxicity of the compounds included in this volume should be addressed to: Joint WHO Secretary of the Joint FAO/WHO Meeting on Pesticide Residues, International Programme on Chemical Safety, World Health Organization, 20 Avenue Appia, 1211 Geneva, Switzerland.









    See Also:
       Toxicological Abbreviations